Checkpoint Signalling: Mad2 Conformers and Signal Propagation

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Checkpoint Signalling: Mad2 Conformers and Signal Propagation

The spindle checkpoint protein Mad2 has a tendency to form multimers and adopts at least two structural conformations. New work highlights the importance of the Mad2-Mad2 interaction, and suggests how spindle checkpoint signals are propagated away from kinetochores.

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The spindle assembly checkpoint (SAC) coordinates mitotic progression with sister chromatid alignment. In mitosis, the checkpoint machinery accumulates at kinetochores, which are scaffolds devoted to microtubule capture. The checkpoint protein Mad2 (mitotic arrest deficient 2) adopts two conformations: open (O-Mad2) and closed (C-Mad2). C-Mad2 forms when Mad2 binds its checkpoint target Cdc20 o...

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Mad1 contribution to spindle assembly checkpoint signalling goes beyond presenting Mad2 at kinetochores

The spindle assembly checkpoint inhibits anaphase until all chromosomes have become attached to the mitotic spindle. A complex between the checkpoint proteins Mad1 and Mad2 provides a platform for Mad2:Mad2 dimerization at unattached kinetochores, which enables Mad2 to delay anaphase. Here, we show that mutations in Bub1 and within the Mad1 C-terminal domain impair the kinetochore localization ...

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Chromosomal Instability: Mad2 beyond the Spindle Checkpoint

What specific defects can cause chromosomal instability in cancer cells? Overexpression of the mitotic checkpoint protein Mad2 triggers chromosome missegregation but, surprisingly, Mad2 exerts this effect through a previously unknown effect on microtubule dynamics.

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The Mad1/Mad2 Complex as a Template for Mad2 Activation in the Spindle Assembly Checkpoint

BACKGROUND The spindle assembly checkpoint (SAC) imparts fidelity to chromosome segregation by delaying anaphase until all sister chromatid pairs have become bipolarly attached. Mad2 is a component of the SAC effector complex that sequesters Cdc20 to halt anaphase. In prometaphase, Mad2 is recruited to kinetochores with the help of Mad1, and it is activated to bind Cdc20. These events are linke...

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ژورنال

عنوان ژورنال: Current Biology

سال: 2005

ISSN: 0960-9822

DOI: 10.1016/j.cub.2005.02.008